Plasma biomarkers in patients with familial cavernous malformation and their first-degree relatives.

Background: We aimed to explore the differences in plasma biomarker levels between patients with familial cerebral cavernous malformations (FCCM) and their healthy first-degree relatives (FDRs) and between FCCM patients with and without severe chronic disease aggressiveness (CDA). Methods: Magnetic resonance imaging (MRI) scanning and genetic testing was performed in patients with multiple CCMs and their FDRs. Sixty-seven plasma biomarkers were tested using a customised multiplex bead immunoassay kit. Univariate and multivariate unconditional logistic regression analyses were conducted to determine the associations between plasma factors and the risk of developing FCCM and severe CDA. Receiver operating characteristic (ROC) curves were generated for each independent risk factor. Results: Plasma factors of 37 patients with FCCM and 37 FDRs were examined. Low CD31 (P < 0.001) and BDNF levels (P = 0.013) were independent risk factors for FCCM. The best model was achieved by combining the results of CD31 and BDNF (AUC = 0.845, sensitivity 0.838, specificity 0.784, cutoff score - 4.295) to distinguish patients with FCCM from healthy FDRs. Low serpin E1/PAI-1 (P = 0.011) and high ROBO4 levels (P = 0.013) were independent risk factors for severe CDA in patients with FCCM. The best model was achieved by combining the results of E1/PAI-1 and ROBO4 levels (AUC = 0.913, sensitivity 1.000, specificity 0.760, cutoff score - 0.525) to identify patients with FCCM and severe CDA. Conclusions: The plasma concentrations of CD31 and BDNF seem to be lower in patients with FCCM than in their healthy FDRs. Low serpin E1/PAI-1 and high ROBO4 concentrations may be correlated with high lesion burden and risk of recurrent bleeding.

Binary split fluorescent biosensor based on lettuce DNA aptamer for label-free and enzyme-free analysis of hepatitis B viral DNA.

Hepatitis B virus (HBV) acts as a severe public health threat, causing chronic liver diseases. Although the quantified evaluation of HBV infection can be obtained by estimating the capacity of the HBV DNA genome, it still lacks an effective and robust detection method without using enzymes or chemical labeling. Herein, we have designed a binary split fluorescent DNA aptasensor (bsFDA) by rationally splitting the lettuce aptamer into two functional DNA short chains and utilizing the HBV DNA segment complementary sequences (HDs). In this strategy, the bsFDA has been investigated to specifically recognize the HDs, forming a triplex DNA with the lettuce aptamer structure. Meanwhile, the turn-on fluorescence of bsFDA is obtained upon formation of a fluorescent complex between DFHO and the triplex DNA structure, allowing the enzyme-free, label-free, fast-responsive, and reliable fluorescence readout for detecting HDs and the potential HDs mutants. Moreover, bsFDA has been applied for spiked HDs analysis in different real matrixes, including human serum and cell lysate. The satisfactory recovery rates and reproducibility of the bsFDA reveal its potential detection efficacy for HDs analysis in biological samples. Overall, bsFDA holds great potential in developing functionalized aptasensors and realizing viral genome analysis in biological research.

Prevalence, genetic and clinical characteristics in first-degree relatives of patients with familial cerebral cavernous malformations in China.

OBJECTIVE: This study aims to investigate the prevalence of familial cerebral cavernous malformations (FCCMs) in first-degree relatives (FDRs) using familial screening, to describe the distribution of initial symptoms, lesion count on cranial MRI and pathogenic gene in patients. METHODS: Patients with multiple CCMs who enrolled from the Treatments and Outcomes of Untreated Cerebral Cavernous Malformations in China database were considered as probands and FDRs were recruited. Cranial MRI was performed to screen the CCMs lesions, and whole-exome sequencing was performed to identify CCM mutations. MRI and genetic screening were combined to diagnose FCCM in FDRs, and the results were presented as prevalence and 95% CIs. The Kaplan-Meier (KM) method was used to calculate the cumulative incidence of FCCM. RESULTS: 33 (76.74%) of the 43 families (110 FDRs) were identified as FCCM (85 FDRs). Receiver operating characteristic analysis revealed three lesions on T2-weighted imaging (T2WI) were the strong indicator for distinguishing probands with FCCM (sensitivity, 87.10%; specificity, 87.50%). Of the 85 FDRs, 31 were diagnosed with FCCM, resulting in a prevalence of 36.5% (26.2%-46.7%). In families with FCCMs, the mutation rates for CCM1, CCM2 and CCM3 were 45.45%, 21.21% and 9.09%, respectively. Furthermore, 53.13% of patients were asymptomatic, 17.19% were intracranial haemorrhage and 9.38% were epilepsy. The mean age of symptom onset analysed by KM was 46.67 (40.56-52.78) years. CONCLUSION: Based on MRI and genetic analysis, the prevalence of CCMs in the FDRs of families with FCCMs in China was 36.5%. Genetic counselling and MRI screening are recommended for FDRs in patients with more than three CCM lesions on T2WI.

Effects of esketamine on postoperative fatigue syndrome in patients after laparoscopic resection of gastric carcinoma: a randomized controlled trial.

BACKGROUND: Despite the implementation of various postoperative management strategies, the prevalence of postoperative fatigue syndrome (POFS) remains considerable among individuals undergoing laparoscopic radical gastrectomy. While the N-methyl-D-aspartic acid receptor antagonist esketamine has demonstrated efficacy in enhancing sleep quality and alleviating postoperative pain, its impact on POFS remains uncertain. Consequently, the objective of this study is to ascertain whether perioperative administration of esketamine can effectively mitigate the occurrence of POFS in patients undergoing laparoscopic radical gastrectomy. METHODS: A total of 133 patients diagnosed with gastric cancer were randomly assigned to two groups, namely the control group (Group C) (n = 66) and the esketamine group (Group E) (n = 67), using a double-blind method. The Group C received standardized anesthesia, while the Group E received esketamine in addition to the standardized anesthesia. The primary outcome measure assessed was the Christensen fatigue score at 3 days after the surgical procedure, while the secondary outcomes included the disparities in postoperative fatigue, postoperative pain, sleep quality, and adverse reactions between the two groups. RESULTS: In the group receiving esketamine, the fatigue scores of Christensen on the third day after surgery were significantly lower compared to the Group C (estimated difference, -0.70; 95% CI, -1.37 to -0.03; P = 0.040). Additionally, there was a significant decrease in the occurrence of fatigue in the Group E compared to the Group C on the first and third days following surgery (P < 0.05). Also, compared to individuals who had distal gastrectomy, those who had entire gastrectomy demonstrated a higher degree of postoperative tiredness reduction with esketamine. Furthermore, the Group E exhibited reduced postoperative pain and improved sleep in comparison to the Group C. Both groups experienced similar rates of adverse events. CONCLUSIONS: The use of esketamine during the perioperative period can improve POFS after laparoscopic radical gastrectomy, without adverse reactions. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2300072167) on 05/06 /2023.